Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection.
Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection.
复制标题
DOI：
10.1371/journal.pone.0015177
复制
发表时间：
2010-12-02
期刊：
影响因子：
3.7
通讯作者：
Daum RS
中科院分区：
文献类型：
--
作者：
Montgomery CP;Boyle-Vavra S;Daum RS
由于USA300遗传背景的出现，CA-MRSA感染已在美国流行。在坏死性肺炎和皮肤感染的实验模型中，与其他 CA 和 HA-MRSA 菌株相比，USA300 分离株具有高毒力。有趣的是，USA300 分离株的核心基因组全局调节和毒力因子基因（包括 agr 和 saeRS）的表达也有所增加。为了检验 agr 和 saeRS 促进观察到的 USA300 的高毒力表型的假设，在 USA300 中构建了各自的等基因缺失突变体。分别通过半定量实时逆转录酶 PCR (qRT-PCR) 和蛋白质印迹评估基因缺失对选定下游毒力基因的表达和蛋白质丰度的影响。还在坏死性肺炎和皮肤感染的小鼠模型中评估了基因缺失的影响。 saeRS 以及较小程度的 agr 的缺失，导致编码 α-溶血素 (hla) 和 Panton-Valentine 杀白细胞素 (lukSF-PV) 的基因表达减弱。尽管 hla 转录存在差异，但在任一缺失突变体的培养物上清液中均检测不到毒素。删除 agr（而非 saeRS）显着增加了编码蛋白 A (spa) 的基因的表达，这与蛋白质丰度的增加相关。在坏死性肺炎和皮肤感染的小鼠模型中，与野生型 USA300 相比，每个缺失突变体均表现出毒力显着减弱。我们得出的结论是，agr 和 saeRS 各自独立地导致了 USA300 的显着毒力，可能是通过它们对分泌毒素表达的影响而实现的。
CA-MRSA infection, driven by the emergence of the USA300 genetic background, has become epidemic in the United States. USA300 isolates are hypervirulent, compared with other CA- and HA-MRSA strains, in experimental models of necrotizing pneumonia and skin infection. Interestingly, USA300 isolates also have increased expression of core genomic global regulatory and virulence factor genes, including agr and saeRS. To test the hypothesis that agr and saeRS promote the observed hypervirulent phenotype of USA300, isogenic deletion mutants of each were constructed in USA300. The effects of gene deletion on expression and protein abundance of selected downstream virulence genes were assessed by semiquantitative real-time reverse-transcriptase PCR (qRT-PCR) and western blot, respectively. The effects of gene deletion were also assessed in mouse models of necrotizing pneumonia and skin infection. Deletion of saeRS, and, to a lesser extent, agr, resulted in attenuated expression of the genes encoding α-hemolysin (hla) and the Panton-Valentine leukocidin (lukSF-PV). Despite the differences in hla transcription, the toxin was undetectable in culture supernatants of either of the deletion mutants. Deletion of agr, but not saeRS, markedly increased the expression of the gene encoding protein A (spa), which correlated with increased protein abundance. Each deletion mutant demonstrated significant attenuation of virulence, compared with wild-type USA300, in mouse models of necrotizing pneumonia and skin infection. We conclude that agr and saeRS each independently contribute to the remarkable virulence of USA300, likely by means of their effects on expression of secreted toxins.
登录
查看更多内容
DOI：
10.1086/650204
发表时间：
2010-02-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Lee MH;Arrecubieta C;Martin FJ;Prince A;Borczuk AC;Lowy FD
通讯作者：
Lowy FD
影响因子：
6.4
作者：
Diep, Binh An;Stone, Gregory G.;Chambers, Henry F.
通讯作者：
Chambers, Henry F.
影响因子：
3.7
作者：
Diep, Binh An;Palazzolo-Ballance, Amy M.;Chambers, Henry F.
通讯作者：
Chambers, Henry F.
DOI：
10.1111/j.1469-0691.2008.02648.x
发表时间：
2009-02
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Brown EL;Dumitrescu O;Thomas D;Badiou C;Koers EM;Choudhury P;Vazquez V;Etienne J;Lina G;Vandenesch F;Bowden MG
通讯作者：
Bowden MG
影响因子：
3.1
作者：
GILLASPY, AF;HICKMON, SG;SMELTZER, MS
通讯作者：
SMELTZER, MS